Induced Sézary syndrome PBMCs poorly express immune response genes up-regulated in stimulated memory T cells

BackgroundDysfunctions in memory T cells contribute to various inflammatory autoimmune diseases and neoplasms. We hypothesize that investigating the differences of genetic profiles between resting and activated naïve and memory T cells may provide insight into the characterization of abnormal memory T cells in diseases, such as Sézary syndrome (SS), a neoplasm composed of CD4+ CD45RO+ cells.ObjectiveWe determined genes distinctively expressed between resting and activated naive and memory cells. Levels of up-regulated genes in resting and activated memory cells were measured in SS PBMCs, which were largely comprised of CD4+ CD45RO+ cells, to quantitatively assess how different Sézary cells were from memory cells.MethodsWe compared gene expression profiles using high-density oligo-microarrays between resting and activated naïve and memory CD4+ T cells. Differentially expressed genes were confirmed by qRT-PCR and immunoblotting. Levels of genes up-regulated in activated and resting memory T cells were determined in SS PBMCs by qRT-PCR.ResultsActivated memory cells expressed greater numbers of immune-mediated genes involved in effector function compared to naïve cells in our microarray analysis and qRT-PCR. Nine out of 14 genes with enhanced levels in activated memory cells had reduced levels in SS PBMCs (p < 0.05).ConclusionsActivation of memory and naïve CD4+ T cells revealed a diverging gap in gene expression between these subsets, with memory cells expressing immune-related genes important for effector function. Many of these genes were markedly depressed in SS patients, implying Sézary cells are markedly impaired in mounting immune responses compared to memory cells.